PerBrain: a multimodal approach to personalized tracking of evolving state-of-consciousness in brain-injured patients: protocol of an international, multicentric, observational study.

BACKGROUND: Disorders of consciousness (DoC) are severe neurological conditions in which consciousness is impaired to various degrees. They are caused by injury or malfunction of neural systems regulating arousal and awareness. Over the last decades, major efforts in improving and individualizing diagnostic and prognostic accuracy for patients affected by DoC have been made, mainly focusing on introducing multimodal assessments to complement behavioral examination. The present EU-funded multicentric research project "PerBrain" is aimed at developing an individualized diagnostic hierarchical pathway guided by both behavior and multimodal neurodiagnostics for DoC patients. METHODS: In this project, each enrolled patient undergoes repetitive behavioral, clinical, and neurodiagnostic assessments according to a patient-tailored multi-layer workflow. Multimodal diagnostic acquisitions using state-of-the-art techniques at different stages of the patients' clinical evolution are performed. The techniques applied comprise well-established behavioral scales, innovative neurophysiological techniques (such as quantitative electroencephalography and transcranial magnetic stimulation combined with electroencephalography), structural and resting-state functional magnetic resonance imaging, and measurements of physiological activity (i.e. nasal airflow respiration). In addition, the well-being and treatment decision attitudes of patients' informal caregivers (primarily family members) are investigated. Patient and caregiver assessments are performed at multiple time points within one year after acquired brain injury, starting at the acute disease phase. DISCUSSION: Accurate classification and outcome prediction of DoC are of crucial importance for affected patients as well as their caregivers, as individual rehabilitation strategies and treatment decisions are critically dependent on the latter. The PerBrain project aims at optimizing individual DoC diagnosis and accuracy of outcome prediction by integrating data from the suggested multimodal examination methods into a personalized hierarchical diagnosis and prognosis procedure. Using the parallel tracking of both patients' neurological status and their caregivers' mental situation, well-being, and treatment decision attitudes from the acute to the chronic phase of the disease and across different countries, this project aims at significantly contributing to the current clinical routine of DoC patients and their family members. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04798456 . Registered 15 March 2021 - Retrospectively registered.

Effect of robotic tilt table verticalization on recovery in patients with disorders of consciousness: a randomized controlled trial.

Verticalization is a common therapeutic intervention during rehabilitation of patients with disorders of consciousness (DoC). The Erigo®Pro is a robotic tilt-table (RTT) with built-in stepping unit for the lower extremities to prevent orthostatic hypotension during verticalization. In addition, the system also provides functional electrical stimulation (FES) of muscles of the lower extremities. In this randomized controlled clinical trial (RCT), 47 patients with subacute DoC received a 4-week verticalization regime (16 verticalization sessions) and were allocated to one of three experimental groups: (1) verticalization by means of RTT with FES, (2) by means of RTT without FES, or (3) by conventional physiotherapy (CPT). Level of consciousness (LoC), spasticity, functional independence in daily activities, and functional brain connectivity measured by means of high-density quantitative EEG were assessed at baseline, directly after the verticalization program and after 6 months. There was a similar clinical improvement in all three experimental groups. RTT was not associated with an effect on any of the clinical outcomes. Verticalization or mobilization time during the study period was significantly positively correlated with recovery of consciousness (rho = 0.494, p < 0.001) in the short term and showed a statistical trend at the 6 months follow-up (rho = 0.244, p = 0.078). In conclusion, RTT treatment is not more effective in promoting recovery of consciousness than CPT in subacute DoC patients. Yet, our data suggest, that verticalization may be an important and feasible rehabilitation intervention in this group of patients. ClinicalTrials.gov NCT Number NCT02639481, registered on December 24, 2015.